• Summary
  Click here to print a Quick Reference Guide
• Background
• Clinical Diagnosis
• Investigation
• Treatment
• Non-Antimicrobial Treatment
• Empirical Antimicrobial Treatment
• Directed Antimicrobial Treatment (when microbiology results are known)
• Duration of Treatment
• Treatment Failure

Back to top

A brain abscess is a focal, intra-cerebral infection, which usually begins as an area of cerebritis and develops into a collection of pus surrounded by a well-vascularised capsule. A brain abscess evolves through stages of early, late cerebritis followed by encapsulation. Intraventricular rupture of the brain abscess is associated with high mortality.

A brain abscess is initiated when microorganisms are introduced into the brain tissue following trauma; contiguous pericranial infection; meningitis or haematogenous dissemination from a distant infective focus. In the largest paediatric series (Tekkok 1992) infections involving middle ear, paranasal sinuses, penetrating trauma and congenital cyanotic heart disease were the most common predisposing factors. Haematogenous spread resulting from sepsis is less common.

There are no randomised controlled trials of therapy for children with brain abscess from which to draw recommendations. Available literature is largely retrospective, reviewing predisposing factors, microbiological features, treatment outcomes and prognostic indicators.  Data on children is further limited as these series are based mainly on adults with a small number of children; subset data on children are not available in any of them. Hence the text that follows is based on current practice, expert recommendations and the limited literature.

Advances in neurosurgical techniques, newer antimicrobials and better imaging technologies have facilitated the diagnosis and management of intracranial pyogenic suppurations over past 20 years; however, it still remains a potentially fatal central nervous system infection. Different factors had been described as influencing the outcome in studies including neurological status at admission, (intraventricular rupture of brain abscess) and multiple abscesses. Imaging severity based on number, location, extent of perilesional oedema and midline shift is also an important prognostic indicator (Demir MK 2007). Infancy is recognised as a risk factor for mortality (Tekkok 1992).  Early recognition and management of predisposing conditions is important for improving the overall outcome.

Brain abscesses are frequently polymicrobial, the most common etiologic organisms in clinical series have been microaerophilic Streptococci and anaerobic bacteria. Additional organisms such as Staphylococcus aureus and Enterobacteriaceae are also seen depending on the underlying source. Streptococci, Staphylococci and Proteus were the commonest organisms in one paediatric series (Tekkok 1992).

Back to top

CLINICAL PRESENTATION

The clinical features in patients with an intracranial abscess evolve with time and depend upon the host pathogen interactions and location of the brain abscess.

Headache was the most frequent symptom followed by fever and seizures.  Classical triad of fever, headache and neurological deficit or absence of fever should not be used to exclude the diagnosis of brain abscess. Papilloedema is common, in 61% of Tekkok’s series. The presence of focal neurological findings (e.g., hemiparesis, hemisensory deficits, aphasia, and ataxia) depends on the location of the abscess, and these findings are seen in approximately one-third to one half of cases.

Younger children may present with non-specific features or evidence of central nervous system infection such as meningeal irritation or seizures, they may enter this treatment pathway via guideline for fever and seizure.

Seizures

Seizures occur in 10–72% of patients with brain abscesses and in up to 50–70% of patients treated with surgical excision. In majority of children with brain abscesses, the onset of seizures is delayed, with only 50% occurring within the first year after treatment. Legg et al. reported that initial seizures appear to occur after a longer latency period in children younger than 10 years old. It has been reported that the mean latency period is ~ 3 years and anticonvulsant agents are generally efficacious in controlling seizures.

Back to top

Recommendation: CT head, ideally with contrast administration, is the imaging modality of choice.
[Evidence level B]

Recommendation MRI head may be required in some cases, following discussion with radiology.
[Evidence level D]

CT scanning, preferably with contrast administration, provides a rapid means of detecting brain abscesses, the size, the number, and the location. MRI scanning is superior to CT and helps establishing the diagnosis by early recognition of cerebritis in a small number of cases where a CT scan may miss the diagnosis. Only 3/96 cases were detectable only on MRI (Hakan, 2006). An abscess appears as a ring-enhancing, space occupying lesion.

Brain abscess development can be divided into 4 stages: 1) Early cerebritis (1-4 days); 2) Late cerebritis (4-10 days); 3) Early capsule formation (11- 14 days); and 4) Late capsule formation (> 14 days).  In the earlier phases, a CT scan performed without addition of contrast may show only low-attenuation abnormalities with mass effect. In later phases, a complete peripheral ring may be seen. On CT scans obtained after administration of contrast material, uniform ring enhancement is virtually always present in later phases. In early phases, the capsule will be difficult to visualize via conventional techniques and double contrast CT often is helpful in defining encapsulation of abscess. Metastatic tumours, high-grade gliomas, cerebral infarction, resolving cerebral contusion or haematoma, lymphoma, toxoplasmosis, demyelinating disease and radiation necrosis must be kept in mind as the differential diagnosis for brain abscesses, appearing as ring-enhancing lesions.  113 out of 130 cases (Tekkok 1992) were supratentorial and those related to congenital heart disease had a predilection for left parietal lobe. CT or MRI scan may also reveal an infected source such as a paranasal sinus or an ear infection.

Unfortunately, there are no laboratory data that are pathognomonic of brain abscess. WCC may be normal. CRP is elevated in up to 60% of patients.

Recommendation: The best way to make a microbiological diagnosis is by culturing of abscess material obtained at the time of surgery, which may be aspiration or excision. 
[Evidence Level B]

Recommendation: Pus collected in a sterile universal container (NOT SWAB) should be sent to Microbiology for urgent microscopy, culture and sensitivity.
[Evidence Level C]

Recommendation: Blood cultures should be obtained when a brain abscess is suspected (prior to commencing antimicrobial therapy).
[Evidence Level B]

Haematogenous spread may be the mechanism of CNS infection and a positive blood culture result may help guide therapy and subsequent investigations.

Recommendation: Lumbar puncture (LP) is absolutely contraindicated in any child in whom a brain abscess is suspected because of the potential for CNS herniation.
[Evidence Level C]

Role of imaging in monitoring response to therapy
Recommendation: Provided the child remains stable, repeating CT scans at weekly intervals for 2 weeks and then at fortnightly intervals for a further 1-month to enable re-accumulation of the abscess to be detected at a pre-clinical phase.
[Evidence level D]

CT scans alone are unreliable in measuring response to treatment since radiological changes lag behind both the reduction in size of the cavity and the clinical response. Complete resolution of the abscess and associated abnormal contrast enhancement may take up to 12–16 weeks, and a small area of residual contrast enhancement may be present for up to 6 months after antibiotic therapy alone or in combination with stereotactic aspiration or surgical drainage via craniotomy. The size of the abscess decreases in 1–4 weeks with antibiotic therapy alone or in combination with stereotactic aspiration, and 95% of abscesses that resolve with antibiotic treatment alone demonstrate a reduction in size within a month. (Brook, 2004)

* Abbreviations: CE = contrast enhancement

Back to top

Recommendation: The treatment of brain abscesses should be a team approach, with collaboration between a Microbiologist, neurologist, neuroradiologist and neurosurgeon.
[Evidence level C]

Surgical management
Operative management provides therapeutic and diagnostic benefits in patients with brain abscesses. There is relief of mass effect for larger, encapsulated abscesses, and cultures can be obtained. Typically, abscesses > 2.5 cm require surgical intervention.  The optimal management of intracerebral abscesses varies according to lesion size, location, and stage.  Early aspiration is advocated in infants because of the propensity for early seizures with meningitis and hydrocephalus, all of which may indicate a poor prognosis. Perioperative and postoperative antiepileptic therapy is generally recommended, and the duration of this therapy should be tailored individually taking into account pharmacological interactions with antimicrobials. (Sheehan 2008).

Stereotactic Aspiration
Image-guided stereotactic aspiration with antibiotic irrigation of the abscess cavity is a treatment modality that can be performed in a minimally invasive manner. Stereotactic aspiration can be conducted at any stage of evolution of the abscess, and a biopsy may yield positive cultures in the early cerebritis stage. This technique allows access to multiple and deep-seated abscesses, has a low complication rate, permits a minimal craniotomy, and allows multiple aspirations, if needed.  Stereotactic aspiration has been demonstrated to have a diagnostic yield of 95%. Although minimally invasive, stereotactic aspiration is not without risk, including the development of an intracerebral haematoma and the rupture of the abscess into the ventricle or subarachnoid space.

Craniotomy
Image-guided stereotactic craniotomy for extirpation of the abscess is considered beneficial in some cases of fungal or multiloculated abscesses and in cases of failed resolution after multiple aspirations. In some cases, the abscess can be drained under ultrasonographic guidance after the craniotomy is performed. If the abscess is superficial and located close to the surface of the brain, a small craniotomy or bur hole may be used for abscess drainage. Brain abscesses secondary to traumatic head injuries should be considered strongly for surgical excision because of the possibility of retained foreign bodies and/or bone fragments.  Disadvantages to a craniotomy include its lack of suitability for lesions of the eloquent cortex, abscesses in the cerebritis stage, or those in children considered surgically high risk.

Intraventricular rupture of an abscess, evident due to hydrocephalus and enhancement of ventricular walls, requires surgical debridement, ventricular drainage, and intraventricular and systemic antibiotic treatment. Alterations in the level of consciousness may herald impending herniation and should prompt surgical drainage of the abscess to alleviate mass effect.

Neuroendoscopy
Neuroendoscopic drainage of brain abscesses is another possible treatment for brain abscesses. This technique allows inspecting and directly viewing the aspiration of the purulent collection, unlike stereotactic aspiration in which there is a lack of direct visual control. In addition, multiloculated abscesses could possibly be treated with the endoscopic technique.

Lesion Location
Cerebrum
Stereotactic aspiration may be performed for abscesses in the cerebritis stage. Lesions < 2.5 cm in diameter may be managed with antibiotics and stereotactic aspiration for identification of a microorganism, while a diameter > 2.5 cm may warrant stereotactic aspiration or surgical excision, contingent on proximity to or location within the eloquent cortex. Stereotactic aspiration of deep-seated abscesses may be more appropriate, and judicious management must be used in the treatment of lesions located in critical areas, such as in speech areas and the motor cortex. Large abscesses with a significant mass effect should be decompressed through the safest treatment modality, such as stereotactic aspiration for abscesses located in eloquent areas.

Cerebellum
Cerebellar abscesses are usually resected via craniotomy, especially when the lesion is associated with mass effect, oedema, and/or obstructive hydrocephalus.

Brainstem
Brainstem abscesses are generally treated with stereotactic aspiration and antibiotic therapy, although there are no concrete data about the optimal management.

Management of multiple brain abscess
Stereotactic aspiration or surgical excision should be performed for abscesses larger than 2.5 cm or smaller lesions that are causing a significant mass effect. If there are no abscesses larger than 2.5 cm in diameter, then the largest abscess should be stereotactically aspirated for the purpose of cultures. The duration of the antibiotics course is usually 6–8 weeks and longer for immunocompromised patients. Serial imaging is conducted on a weekly basis or immediately if there is a decline in the patient's neurological status. A decline in the patient's clinical status, enlargement of the abscess after 2 weeks of antibiotics, or lack of reduction in the size of the abscess after 4 weeks of antibiotic therapy should warrant a repeated operation (Mathisen 1997)

Intraventricular rupture of brain abscess
Recommendation: A craniotomy should ideally be performed, the abscess excised and, at the same time, the ventricular system to be “washed out” using normal saline. At the end of the procedure an EVD should be placed so that intrathecal antibiotics can be administered.
[Evidence level C]

Back to top

Recommendation: Initial antimicrobial choice is empirical and should be tailored to cover the most likely pathogens in individual cases depending upon the location of the abscess and predisposing focus (dental, paranasal sinuses, otogenic etc.), according to Table 2.
[Evidence level D]

Recommendation: Wherever possible (e.g. in stable children in whom early surgery/drainage is planned) empirical antimicrobial therapy should be started after surgical drainage, or, if this is not possible, after blood cultures have been taken.
[Evidence level D]

Recommendation: Broad spectrum empirical antimicrobial regimens should be tailored to organism isolated from pus or blood cultures i.e. converted to “directed antimicrobial therapy” whenever possible (see Table 3).
[Evidence level D]

Antimicrobial therapy
No randomized controlled trials of therapies for brain abscess have been conducted because of the relative infrequency of this infection. Appropriate antimicrobial therapy for brain abscess depends on choosing antibiotics that are able to penetrate the abscess cavity and have activity against the suspected pathogens. Although there are considerable data on CSF antimicrobial levels in cases of bacterial meningitis, there is still limited information available on antimicrobial penetration into brain abscess cavities. The blood-CSF and the blood-brain barriers are histologically different and a high degree of CSF penetration does not guarantee penetration into the brain tissue.   

* Use Ceftazidime as third generation cephalosporin if Pseudomonas infection suspected.
Contact Medical Microbiologist for advice if any risk factors for resistant gram negative infections (e.g. previous colonisation, intensive care unit stay, transfer from outside UK)
** Please discuss antibiotic options with Microbiology in cases of penicillin allergy.

There have been a number of more recent case reports demonstrating successful non-operative treatment of brain abscess with antibiotics alone. This approach may be appropriate for clinically stable patients who are poor candidates for surgery or for patients with surgically inaccessible lesions. Small lesions (2 cm) located in the better-vascularised cortical areas are more likely to respond to antibiotics alone. Medical treatment alone should not be used when the diagnosis is in doubt or when pathological confirmations are not available. Serial CT or MRI scans are crucial because abscesses may enlarge despite antibiotic treatment. If neurological deterioration occurs as a consequence of mass effect, surgical removal may become necessary.

The patient can be switched onto oral therapy when: Evidence Level C

• CRP shows downward trend if the patient is otherwise well
• The patient has no signs of fever
• Appropriate oral agents are available
• The patient can tolerate oral antibiotics

Please contact Microbiology to discuss oral antimicrobial options.
Intrathecal administration of antibiotics is not routinely recommended (apart from intraventricular rupture of brain abscess)

Back to top

Recommendation: Broad spectrum empirical antimicrobial regimens should be tailored to organism isolated from pus or blood cultures i.e. converted to “directed antimicrobial therapy” whenever possible (see Table 3).
[Evidence level D]

**Dose adjusted according to estimated creatinine clearance; need to monitor Vancomycin trough levels.

Treatment of Primary Focus
To minimise the risk of recurrent or non-responsive intracranial infection, any identifiable primary source requires aggressive treatment. This may include surgery for paranasal sinuses, middle ear or dental sepsis, physiotherapy and echocardiography in patients with a cardiac source. The timing of such interventions does not need to coincide with intracranial surgery but should be undertaken in an expert, timely fashion.

Back to top

Recommendation: Duration of therapy should be determined by clinical progress, CT findings and whether surgical drainage has been undertaken.
[Evidence level C]

Recommendation: A minimum of 4 weeks treatment (usually 6-8 weeks) is required if the abscess is treated with antibiotics alone (demonstrate resolution of ring enhancing lesions on CT before stopping antibiotics).
[Evidence level C]

Recommendation: Give 3-4 weeks if abscess has been excised and 4-6 weeks if abscess has been aspirated or excised, provided the clinical response is good.
[Evidence level C]

The appropriate duration of antimicrobial therapy for brain abscess remains unclear. A 6–8 week course of parenteral antibiotics has traditionally been recommended provided the aetiological organisms are susceptible and that adequate surgical drainage can be established.  More recently, shorter durations of antibiotic therapy have been proposed based on correlation between clinical progress and CT findings.

Back to top

Recommendation: Discussion between neurosurgery and microbiology is recommended.
[Evidence level D]

Back to top